This program project attempts to provide a coordinated approach to obtaining a detailed understanding of the endocrine regulation of the reproductive cycle and early pregnancy. Integrated, goal-oriented studies will be performed in rats and humans. Precise, sensitive, and specific techniques for protein and steroid hormone determinations, and appropriate methods for in vitro studies of hormone biosynthesis, metabolism, and interaction with target tissues will be employed. Wherein possible, the studies will be performed in non-anesthetized and non-stressed rats and humans using indwelling cannulas to obtain frequent samples of blood for hormone analysis. Attempts will be made to determine factors which stimulate or inhibit the secretion of releasing factors and to determine if the responsiveness of the pituitary gland to such factors varies during the estrous cycle, in the presence or absence of gonadal steroids, and as the result of previous exposure to such factors. Attempts will also be made to "mimic" events of the estrous cycle in rats and the menstrual cycle in humans by steroid replacement following castration, gonadotropin replacement following hypophysectomy, and releasing factor replacement in rats under hypothalamic blockade. Immunohistochemical, autoradiographic, radioimmunoassay and enzymatic studies will be employed to determine the sites and mechanisms of gonadotropins in target tissues.